Prosthetic surgery is aimed to repair impaired organs by replacing with artificial devices or by grafting artificial or native scaffolds for developing into autogenic tissues. Currently more than 10,000 patients undergo heart valve replacement surgery in Japan. Mechanical valves are used in about 7% of the patients and xenogenic valves made from glutaraldehyde-fixed porcine or bovine tissues are used in the balance of patients. In case of mechanical valves, continuous administration of an antithrombotic agent is essential after replacement while affecting patient's quality of life. The xenogenic valves are durable in vivo only for about 15 years due to calcification and requires repeated replacement surgery for young generation.
In case of glutaraldehyde-fixed xenogenic vascular grafts, there exists, in addition to the limited durability due to calcification, another disadvantage. Namely inherent mechanical properties such as tensile strength and elasticity possessed by the native tissue have been lost. Artificial vascular grafts made of biodegradable polymers such as polylactic acid have been clinically used in the venous system of children. However, restenosis and other adverse effects have been reported. In addition, the biodegradable vascular grafts cannot be used in the arterial system because of possible puncture due to the hydrolysis of the polymer.
It is known to prepare scaffold materials for grafting by decellularizing native tissues with enzymes or detergents to obtain extracellular matrix components. However, the decellularized tissues as such do not have a strength sufficient to withstand relatively high pressures required as, for example, the aortic valve. Thus some strengthening treatment such as cross-linking with glutaraldehyde is indispensable. The fixation with glutaraldehyde, however, necessarily diminishes the biodegradability of matrix collagen and the treated tissue thus remains unchanged in the living body such that ingrowth of autogenic cells, which is essential for the regeneration of autogenic tissues, hardly takes place.
JP 5404388B corresponding to U.S. Pat. No. 4,098,571 discloses a process for preparing a xenograft blood vessel substitute comprising enzymatically digesting a porcine blood vessel with chymotrypsin and then fixing the resulting digested blood vessel with a fixing agent such as glutaraldehyde. This blood vessel substitute is intended to use as an artery-vein shunt for accessing to the vascular system of those patients who undergo long term hemodialysis. In this case, ingrowth of patient's own cells into the grafted blood vessel is not essential.
Accordingly, a need remains to exist for a biological scaffold material which is biocompatible in terms of immunogenicity and thrombogenicity, which may be eventually decomposed in the living body but persistent until it is incorporated into the recipient's own tissue, and which allows ingrowth of autogenic cells without calcification.